[unreadable] [unreadable] Lung cancer is the leading cause of cancer-related deaths in both men and women in the US today, responsible for 28% of all cancer-related deaths. Long-term prognosis for patients with advanced stage non- small cell lung cancer, present in 75% of new cases, is dismal with a 9-12 month median survival. Future improvements are likely to come from concurrent combined/adjunctive modality treatments or newer `directed' agents. The application of exogenously induced heat (hyperthermia) has been proposed as an adjunctive agent. Our long-term goal is to develop treatments that are more effective for patients with metastatic lung cancer. Based on our basic science research, we studied and modified a perfusion-based method for delivering heat to the entire body, then proceeded with an FDA-approved phase I study. This redesigned system, resulted in delivery of a documented therapeutic hyperthermic dose with homogenous distribution of heat throughout the body. Serious mechanical deficiencies were noted in the system however, the parent company declared this unit obsolete. Based on our basic science and animal data, and encouraged by the results of the clinical trial, UTMB has decided on further development of a hyperthermia delivery system the objective of this proposal. In order to do so we have partnered with MC3 a research and design company and will address three Specific Aims: Specific Aim 1: Build a working prototype circuit of vv-PISH for the delivery of hyperthermia with the following features: 1) the non-occlusive peristaltic roller pump, 2) an efficient pediatric heat exchanger, 3) a hemofilter selected to achieve adequate ion exchange, and 4) a control system to regulate energy transfer and to monitor the system for safety. Specific Aim 2: The system will be bench-tested for safety and temperature control performance. Specific Aim 3: Apply the new vv-PISH prototype circuit in healthy swine (n=10) to achieve core temperature of 420C for 2 hours then recover the animal, and study the following: 1) safety of new system, 2) efficiency of heat transfer and, 3) stability of serum electrolytes maintained by the vv-PISH device. The immediate goal of this research plan is to address needed improvements in the original design and produce a device capable of delivering predictable therapeutic doses of hyperthermia safely. In phase II, we will perform a prospective, randomized trial comparing current standard of care to current standard of care plus hyperthermia in stage IV lung cancer. The goal of this project is to develop a clinical system for inducing full body hyperthermia to treat metastatic lung cancer. The system is based on a Phase I clinical trial demonstrating the efficacy of such a treatment. [unreadable] [unreadable] [unreadable]